SEOM-GECP-GETTHI Clinical Guidelines for the treatment of patients with thymic epithelial tumours (2021).

Thymic epithelial tumours (TET) represent a heterogeneous group of rare malignancies that include thymomas and thymic carcinoma. Treatment of TET is based on the resectability of the tumour. If this is considered achievable upfront, surgical resection is the cornerstone of treatment. Platinum-based chemotherapy is the standard regimen for advanced TET. Due to the rarity of this disease, treatment decisions should be discussed in specific multidisciplinary tumour boards, and there are few prospective clinical studies with new strategies. However, several pathways involved in TET have been explored as potential targets for new therapies in previously treated patients, such as multi-tyrosine kinase inhibitors with antiangiogenic properties and immune checkpoint inhibitors (ICI). One third of patient with thymoma present an autoimmune disorders, increasing the risk of immune-related adverse events and autoimmune flares under ICIs. In these guidelines, we summarize the current evidence for the therapeutic approach in patients with TET and define levels of evidence for these decisions.

Targeting HER2 in non-small-cell lung cancer (NSCLC): a glimpse of hope? An updated review on therapeutic strategies in NSCLC harbouring HER2 alterations.

Non-small-cell lung cancer (NSCLC) harbouring HER2 alterations is now considered a distinct molecular subtype. The activation of HER2 in NSCLC occurs via three mechanisms, i.e. gene mutation (1%-4% of cases), gene amplification (2%-5%) and protein overexpression (2%-30%), with different prognostic and predictive outcomes. So far, non-selective tyrosine kinase inhibitors (TKIs) have shown a minor benefit in HER2-mutant NSCLC patients with objective response rates (ORRs) ranging from 0% to 19%. Trastuzumab-based chemotherapy was not found to be superior to chemotherapy alone [median progression-free survival (PFS) 6.1 versus 7 months, respectively] and dual HER2 antibody blockade with trastuzumab and pertuzumab had limited efficacy (ORR 13%-21%). In contrast, novel more selective HER2 TKIs such as poziotinib and pyrotinib have shown a promising activity in HER2-mutant pre-treated NSCLC patients, with response rates up to 38% and 44%, respectively. The most encouraging data come from phase II studies that evaluated the antibody-drug conjugates (ADCs) ado-trastuzumab-emtansine and trastuzumab-deruxtecan in patients with HER2-mutant NSCLC, with response rates of 50% and 62%, respectively. These agents are bringing hope to the management of HER2-altered NSCLC. Moreover, a paradigm shift from monotherapies towards combinations of agents with distinct mechanisms of action, such as ADCs with irreversible TKIs or immune checkpoint inhibitors, is already taking place and will change the therapeutic landscape of HER2-driven NSCLC. This paper provides a practical, concise and updated review on the therapeutic strategies in NSCLC with HER2 molecular alterations.

Antibiotic-exposed patients with non-small-cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy.

BACKGROUND: Prior antibiotic therapy (pATB) is known to impair efficacy of single-agent immune checkpoint inhibitors (ICIs), potentially through the induction of gut dysbiosis. Whether ATB also affects outcomes to chemo-immunotherapy combinations is still unknown. PATIENTS AND METHODS: In this international multicentre study, we evaluated the association between pATB, concurrent ATB (cATB) and overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in patients with non-small-cell lung cancer (NSCLC) treated with first-line chemo-immunotherapy at eight referral institutions. RESULTS: Among 302 patients with stage IV NSCLC, 216 (71.5%) and 61 (20.2%) patients were former and current smokers, respectively. Programmed death-ligand 1 tumour expression in assessable patients (274, 90.7%) was ≥50% in 76 (25.2%), 1%-49% in 84 (27.9%) and <1% in 113 (37.5%). Multivariable analysis showed pATB-exposed patients to have similar OS {hazard ratio (HR) = 1.42 [95% confidence interval (CI): 0.91-2.22]; P = 0.1207} and PFS [HR = 1.12 (95% CI: 0.76-1.63); P = 0.5552], compared to unexposed patients, regardless of performance status. Similarly, no difference with respect to ORR was found across pATB exposure groups (42.6% versus 57.4%, P = 0.1794). No differential effect was found depending on pATB exposure duration (≥7 versus <7 days) and route of administration (intravenous versus oral). Similarly, cATB was not associated with OS [HR = 1.29 (95% CI: 0.91-1.84); P = 0.149] and PFS [HR = 1.20 (95% CI: 0.89-1.63); P = 0.222] when evaluated as time-varying covariate in multivariable analysis. CONCLUSIONS: In contrast to what has been reported in patients receiving single-agent ICIs, pATB does not impair clinical outcomes to first-line chemo-immunotherapy of patients with NSCLC. pATB status should integrate currently available clinico-pathologic factors for guiding first-line treatment decisions, whilst there should be no concern in offering cATB during chemo-immunotherapy when needed.

SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019).

Small-cell lung cancer (SCLC) accounts for 15% of lung cancers. Only one-third of patients are diagnosed at limited stage. The median survival remains to be around 15-20 months without significative changes in the strategies of treatment for many years. In stage I and IIA, the standard treatment is the surgery followed by adjuvant therapy with platinum-etoposide. In stage IIB-IIIC, the recommended treatment is early concurrent chemotherapy with platinum-etoposide plus thoracic radiotherapy followed by prophylactic cranial irradiation in patients without progression. However, in the extensive stage, significant advances have been observed adding immunotherapy to platinum-etoposide chemotherapy to obtain a significant increase in overall survival, constituting the new recommended standard of care. In the second-line treatment, topotecan remains as the standard treatment. Reinduction with platinum-etoposide is the recommended regimen in patients with sensitive relapse (≥ 3 months) and new drugs such as lurbinectedin and immunotherapy are new treatment options. New biomarkers and new clinical trials designed according to the new classification of SCLC subtypes defined by distinct gene expression profiles are necessary.

Obstetric intra-operative cell salvage: a review of an established cell salvage service with 1170 re-infused cases.

The use of cell salvage during caesarean section has been increasing steadily, although there are concerns relating to cost, a perceived risk of amniotic fluid embolism, and fetal red cell sensitisation. We present observational data from almost a decade of use of intra-operative cell salvage in obstetrics. By the end of this period, we set up cell salvage collection for > 98% of all caesarean sections. From 2008 to 2017, 1170 women have had a re-infusion of cell salvaged blood with no clinical safety concerns; the median (IQR [range]) volume was 231 (154-306 [80-1690]) ml. During this time there has been a marked reduction in the number of women who were transfused allogeneic blood, as well as the amount of blood transfused. In total, 647 (55%) women have had alloimmunisation testing, with two positive cases. Quality control data indicate that the quality of blood processed from partial first bowls is no worse than that from full bowls. We discuss the costs of providing this service with regard to: staffing costs; single suction; leucodepletion filters; selectivity in the processing of collected blood; and the use of partial first bowls.

Obstetric intra-operative cell salvage and maternal fetal red cell contamination.

BACKGROUND: The significance of fetal red blood cell (RBC) contamination in obstetric intra-operative cell salvage is not fully known. It is unclear if we re-infuse a larger volume of fetal RBCs into the maternal circulation than the amount that occurs secondary to transplacental haemorrhages is unclear. We also do not know if there is a critical volume required to cause alloimmunisation or if larger volumes increase the risk. OBJECTIVES: The aim of this study is to provide data on the level of fetal RBC contamination in the maternal circulation prior to delivery and immediately post-partum and to compare these levels to those found in processed cell-salvaged blood. METHODS: In the first part of this study, we quantified the levels of fetal RBCs circulating in women immediately prior to delivery. This was then repeated with a separate group measuring the levels of fetal RBCs pre- and post-delivery. RESULTS: We found that 37% of women had fetal cells detected in their circulation, median 0·00 mL (IQR 0-0·24; average 0·3 mL, maximum 4·56 mL). Fetal RBCs were present pre-delivery (maximum 0·66 mL) in 16% of women, increasing to 53% post-delivery (median 0·66 mL; IQR 0·22-2·20, maximum 21·20 mL). CONCLUSIONS: We have shown that fetal RBCs are present in the maternal circulation throughout pregnancy and that the volumes are comparable to that obtained from intra-operative salvage, with contamination amounts of up to 19 mL. At the Royal Cornwall Hospital, our experience and evidence supports offering intra-operative salvage to all women, and we have not noted an increase in antibody formation, compared to allogeneic transfusion.

KRAS genetic variant as a prognostic factor for recurrence in resectable non-small cell lung cancer.

PURPOSE: Several angiogenic prognostic markers are under investigation because of their potential clinical utility, aiming to improve patient outcomes. We hypothesized that genetic variant in the VEGF pathway could be used as prognostic markers of survival in non-small cell lung cancer (NSCLC) patients undergoing pulmonary resection. METHODS: We evaluated the relationship between genetic variants in the VEGF pathway and relapse-free survival (RFS, main endpoint) and overall survival (OS, secondary endpoint) among 131 patients with stage I-III NSCLC treated with surgical resection from 2009 to 2013. Clinical, pathological and surgical data were prospectively collected. Twenty-five variants in sixteen relevant genes were selected and genotyped in tumor samples by real time PCR. The Kaplan-Meier method with the log-rank test and Cox's regression models were used for RFS and OS analyses. RESULTS: With a median follow-up of 36 (min = 2.8; max = 67.4) months, there were 31 (24%) relapses and 31 (24%) deaths. Overall, median RFS was not reached and median OS was 65 [95% confidence interval (CI) 56-75] months. The KRAS rs1137282 and PIK3C2A rs4356203 variants were significantly associated with RFS. For KRAS rs1137282, the 3-year RFS was 76% [95% CI 64-84%] in patients harboring an A/A genotype compared to 53% [95% CI 37-69%] in patients harboring an A/G or G/G genotype (p = 0.02). For PIK3C2A rs4356203, patients with an A/A or an A/G genotype had a 3-year RFS of 72% [95% CI 58-76%], whereas in patients with a G/G genotype was 49% [95% CI 28-70%] (p = 0.02). These associations remained statistically significant after adjusting for all the relevant clinical parameters in the multivariable analysis. CONCLUSION: Genetic variants in VEGF pathway may be associated with recurrence in stage I-III NSCLC. Specifically, the KRAS rs1137282 could be considered as a prognostic factor for recurrence in resectable NSCLC patients. Although PIK3C2A rs4356203 was associated with RFS, further analyses are necessary to confirm these data.

A Study of the Patients Admitted to the Clinical Decision Unit over One Year.

Clinical decision units (CDUs) are areas within an emergency department (ED) providing care for the patient who may benefit from an extended observation period, usually for a maximum of twenty-four hours. A retrospective patient record audit was performed to determine the characteristics of patients admitted to the Cork University Hospital (CUH) CDU over 12 months. The average length of stay of a patient in the CDU was 29 hours. The most common diagnoses admitted to the CDU were chest pain (9.5%) and headache (7.2%). The research implies that the CDU provided a means for CUH to save approximately €2 million annually.

Is cell salvaged vaginal blood loss suitable for re-infusion?

BACKGROUND: Haemorrhage is one of the commonest causes of maternal critical care admission. Cell salvage used during caesarean section can contribute to a reduction in allogeneic blood consumption. This study sought to provide a practical method to salvage blood lost after vaginal delivery and a description of the constituents before and after washing. METHODS: Blood lost after vaginal delivery was collected from 50 women and washed in a cell salvage machine. No blood was re-infused to any patient in this study. The following measurements were made pre- and post-wash: haemoglobin (haematocrit), alpha-fetoprotein, albumin, lactate dehydrogenase, plasma free haemoglobin, heparin concentration, fetal red cells and identification of bacterial species and colony-forming units (cfu). RESULTS: Median haemoglobin concentration post-wash was 15.4 g/dL. Alpha-fetoprotein, lactate dehydrogenase and albumin concentrations were significantly reduced post-wash (<1 KU/L, 183 IU/L, 0.011 g/L, respectively; P <0.001). Median fetal red cell level post-wash was 0.15 mL [range 0-19 mL]. Median bacterial contamination concentration post-wash was 2 cfu/mL, with a median total count of 303 cfu. CONCLUSIONS: Vaginal blood can be collected efficiently with little disruption to patient management. The amounts of haemolysis and washout of non-red cell blood components are consistent with results in our cell salvage quality assurance programme for caesarean section and non-obstetric surgery. Although bacteria are detectable in all the post-wash and post-filter samples, the median residual contamination is similar to that found with cell salvage in caesarean section, and if re-infused would result in a circulating bacteraemia of <1 cfu/mL; this is similar to that seen with dental procedures (0.3-4.0 cfu/mL) and is thought to be clinically insignificant.

Is there a limit for the laparoscopic approach of a retroperitoneal residual mass postchemotherapy?

OBJECTIVES: Rescue lymphadenectomy for testicular cancer is a complex surgery, with a high number of complications. The laparoscopic approach appears to offer faster recovery and improved quality of life compared with open surgery. The aim of our study is to report on our experience and to define whether there is a limit (oncological, anatomical or technical) for laparoscopic management. MATERIAL AND METHODS: A retrospective study was conducted of 15 patients who underwent laparoscopic retroperitoneal lymphadenectomy after chemotherapy. In addition to epidemiological and oncologic variables, we analyzed the mean surgical time, intraoperative and postoperative complications, the mean hospital stay and the mean follow-up time. RESULTS: The mean surgical time was 294 minutes (range, 180-240). There were 4 large-vessel vascular lesions, all of which were large-volume retroperitoneal masses, with diameters >7 cm. The rate of postoperative complications was 33%; there was only 1 case of Clavien >III. The mean hospital stay was 5.38 days (range, 2-9), and the mean patient follow-up was 28.9 months (range, 1-79). There was no recurrence in any of the cases. CONCLUSIONS: The laparoscopic approach is an oncologically safe option for the rescue treatment of testicular cancer. The complex location of these masses entails the onset of severe intraoperative complications. We have observed a clear relationship between vascular complications and large masses (>7 cm). We therefore believe that it would be appropriate to establish a limit on the size for laparoscopic treatment.

EGFR ligands and DNA repair genes: genomic predictors of complete response after capecitabine-based chemoradiotherapy in locally advanced rectal cancer.

Epidermal growth factor receptor (EGFR) activation by radiation leads to increased cell proliferation and acts as a radioresistance mechanism. Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer, and to date, no biomarkers of response have been found. We analyzed polymorphisms in the EGFR and its ligands, DNA repair genes and the thymidylate synthase in 84 stages II and III rectal cancer patients treated with neoadjuvant capecitabine plus radiotherapy. The rs11942466 polymorphism in the amphiregulin (AREG) gene region was associated with a pathological complete response (ypCR) (odds ratio: 0.26; 95% confidence interval: 0.06-0.79; P=0.014). The rs11615 C>T polymorphism in the ERCC1 gene also correlated with the ypCR as no patients with a C/C genotype achieved ypCR; P=0.023. This is the first work to propose variants within the AREG and the ERCC1 genes as promising predictive biomarkers of ypCR in rectal cancer.

Assessment of intra-operative cell salvage haemolysis in the obstetric and orthopaedic clinical setting, in comparison with allogeneic blood.

OBJECTIVES/BACKGROUND: Haemolysis is still a re-occurring theme in intra-operative cell salvage (ICS) with further haemolysis possibly caused by suction pressure, washing/centrifuging process and aspiration method. Previous investigations, along with manufacturer's reports, state that between 75 and 95% of free haemoglobin (Hb) is removed by the washing and centrifugation process; however, if these results are above the expected levels, excess free Hb may remain after washing. The aim of this article was to quantify haemolysis levels whilst employing different aspiration methods from skimmed (orthopaedics) and pooled (obstetrics) surgery types and comparing this to allogeneic blood. METHODS/MATERIALS: Samples obtained from 50 allogeneic units and 50 ICS cases (25 obstetric and 25 orthopaedic) were tested for plasma free Hb levels. RESULTS: Free Hb testing as a marker of haemolysis was greatest in orthopaedic 17·2 g L(-1) (range: 1·7-57·0 g L(-1) ), obstetric 2·8 g L(-1) (range: 1·0-13·5 g L(-1) ) and allogeneic 0·95 g L(-1) (range: 0·2-4·8 g L(-1) ) cases. CONCLUSION: ICS involving skimming collection techniques (orthopaedics) had significantly more haemolysis than pooled collections (obstetrics) (P < 0·001). Further analysis of orthopaedic data highlighted a difference between the three machines used with the Haemonetics OrthoPat (Haemonetics Ltd., Watford, UK) significantly higher with a free Hb of 29·8 g L(-1) compared with the other two machines 6·7 g L(-1) (P < 0·001). On comparison of ICS blood to allogeneic blood, free Hb levels obtained from ICS were significantly higher (P < 0·001).

Chemotactic clusters in confined run-and-tumble bacteria: a numerical investigation.

We present a simulation study of pattern formation in an ensemble of chemotactic run-and-tumble bacteria, focussing on the effect of spatial confinement, either within traps or inside a maze. These geometries are inspired by previous experiments probing pattern formation in chemotactic strains of E. coli under these conditions. Our main result is that a microscopic model of chemotactic run-and-tumble particles which themselves secrete a chemoattractant is able to reproduce the main experimental observations, namely the formation of bacterial aggregates within traps and in dead ends of a maze. Our simulations also demonstrate that stochasticity plays a key role and leads to a hysteretic response when the chemotactic sensitivity is varied. We compare the results of run-and-tumble particles with simulations performed with a simplified version of the model where the active particles are smooth swimmers which respond to chemotactic gradients by rotating towards the source of chemoattractant. This class of models leads again to aggregation, but with quantitative and qualitative differences in, for instance, the size and shape of clusters.

Lactate dehydrogenase and Haemolysis Index as quality control markers of haemolysis in intra-operative cell salvage.

OBJECTIVES: The aim of this investigation was to explore the potential use of the tests lactate dehydrogenase (LDH) and Haemolysis Index as haemolysis markers in intra-operative cell salvage (ICS) blood in comparison to plasma free haemoglobin levels. BACKGROUND: Quality control (QC) should be seen as a fundamental part of any ICS blood conservation programme, however, due to lack of available knowledge, familiarity and experience, QC is still a comparatively new subject. A QC pilot scheme is currently being undertaken by the Royal Cornwall Hospital in association with the UK Cell Salvage Action Group to explore potential markers that can be used to assess the quality of blood obtained from ICS. This test list should be available to all ICS users and achievable within financial budgets. Currently this proposed test list includes a full blood count, a protein marker such as urine albumin/microalbumin and heparin monitoring. Haemolysis testing is another key marker. METHODS/MATERIALS: Samples were collected from ICS processed blood and allogeneic SAGM leucodepleted red cell units and processed for plasma free haemoglobin, LDH and Haemolysis Index. RESULTS: There was a very strong correlation between plasma free haemoglobin and LDH (0.960), and plasma free haemoglobin and the Haemolysis Index (0.944). CONCLUSION: We have shown that the LDH and Haemolysis Index tests are suitable and reliable alternatives for measuring haemolysis from samples obtained from ICS or allogeneic blood. We have incorporated the LDH test into our Hospital's ICS QC package and recommend that this test is considered for all ICS QC samples.

Adult Dental Health Survey 2009: relationships between dental attendance patterns, oral health behaviour and the current barriers to dental care.

The importance of understanding barriers to dental attendance of adults in the UK was acknowledged in the first Adult Dental Health Survey in 1968 and has been investigated in all subsequent ADH surveys. In 1968, approximately 40% of dentate adults said they attended for a regular check-up; by 2009 this was 61%. Attendance patterns were associated with greater frequency of toothbrushing, use of additional dental hygiene products, lower plaque and calculus levels. Just under three-fifths of adults said they had tried to make an NHS dental appointment in the previous five years. The vast majority (92%) successfully received and attended an appointment, while a further 1% received an appointment but did not attend. The remaining 7% of adults were unable to make an appointment with an NHS dentist. The majority of adults were positive about their last visit to the dentist, with 80% of adults giving no negative feedback about their last dentist visit. Cost and anxiety were important barriers to care. Twenty-six percent of adults said the type of treatment they had opted for in the past had been affected by the cost and 19% said they had delayed dental treatment for the same reason. The 2009 survey data demonstrated a relationship between dental anxiety and dental attendance. Adults with extreme dental anxiety were more likely to attend only when they had trouble with their teeth (22%) than for a regular check-up.

Adult Dental Health Survey 2009: transformations in British oral health 1968-2009.

This series of four papers reports and interprets the findings of the Adult Dental Health Survey (ADHS), 2009, published in early 2011. This is the fifth in a series of surveys repeated every decade since 1968. The evolution of the surveys and the way the supporting methodology has changed to meet the changing needs and circumstances over the last 40 years is described. In 1968, 37% of adults in England and Wales were edentate. By 2009, only 6% of the combined population of England, Wales and Northern Ireland were edentate. Among the dentate in 1968, there were a mean of 21.9 teeth. By 2009, not only had the dentate increased by 30 percentage points as a fraction of the population, but the number of teeth in this group had also increased by nearly four teeth on average to 25.7. There were significant variations in oral health according to geography and social variables and smaller differences according to sex. The retention of 21 or more teeth is widely used as a way of defining a minimum functional dentition. The proportion of adults with 21+ teeth increased from 73% in 1978 to 86% in 2009. Further huge improvements are projected as younger generations age, assuming future tooth loss continues at current low rates. We might expect that over 90% of those aged 35-44 in 2009 have a realistic prospect of retaining a functional natural dentition of 21 or more teeth by age 80.

Exposure to the common food additive carrageenan leads to glucose intolerance, insulin resistance and inhibition of insulin signalling in HepG2 cells and C57BL/6J mice.

AIMS/HYPOTHESIS: The aim of this study was to determine the impact of the common food additive carrageenan (E407) on glucose tolerance, insulin sensitivity and insulin signalling in a mouse model and human hepatic cells, since carrageenan is known to cause inflammation through interaction with toll-like receptor (TLR)4, which is associated with inflammation in diabetes. METHODS: Male C57BL/6J mice were given carrageenan (10 mg/l) in their drinking water, and underwent a glucose tolerance test (GTT), an insulin tolerance test (ITT) and an ante-mortem intraperitoneal insulin injection. HepG2 cells were exposed to carrageenan (1 mg/l × 24 h) and insulin. Levels of phospho(Ser473)-protein kinase B (Akt), phospho(Ser307)-IRS1, phosphoinositide 3-kinase (PI3K) activity and phospho(Ser32)-inhibitor of κB (IκBα) were determined by western blotting and ELISA. RESULTS: Glucose tolerance was significantly impaired in carrageenan-treated 12-week-old mice compared with untreated controls at all time points (n = 12; p < 0.0001). Baseline insulin and insulin levels at 30 min after taking glucose during the GTT were significantly higher following carrageenan treatment. During the ITT, glucose levels declined by more than 80% in controls, but not in carrageenan-treated mice. Carrageenan exposure completely inhibited insulin-induced increases in phospho-(Ser473)-Akt and PI3K activity in vivo in mouse liver and in human HepG2 cells. Carrageenan increased phospho(Ser307)-IRS1 levels, and this was blocked when carrageenan-induced inflammation was inhibited. CONCLUSION: This is the first report of the impact of carrageenan on glucose tolerance and indicates that carrageenan impairs glucose tolerance, increases insulin resistance and inhibits insulin signalling in vivo in mouse liver and human HepG2 cells. These effects may result from carrageenan-induced inflammation. The results demonstrate extra-colonic manifestations of ingested carrageenan and suggest that carrageenan in the human diet may contribute to the development of diabetes.

A modified thrombin clotting time test as a quality control marker for heparin contamination in obstetric intraoperative cell salvage.

OBJECTIVE: To assess if a modified thrombin clotting time test could be used as a simple quality control (QC) method to screen for unfractionated heparin in the product obtained from obstetric intraoperative cell salvage cases before re-infusion. BACKGROUND: A national QC scheme has recently been piloted to monitor the quality of autologous blood being returned to the patient. Laboratory tests include full blood count and microalbumin. Unfractionated heparin testing should be performed to ensure that there is no gross contamination of heparin in the final product; however, presently, there is no quick cheap test available suitable for heparin detection. MATERIALS AND METHODS: Samples were collected into plain non-anticoagulated tubes and centrifuged at 2500 × g for 5 min. Supernatant was mixed with commercially available coagulated normal plasma and a thrombin clotting time test performed. RESULTS: Calibration runs demonstrated that our system was sensitive up to 0 · 14 IU mL(-1) heparin, linear between 0 · 08 and 0 · 14 IU mL(-1). CONCLUSION: We have shown that the thrombin clotting time test can be modified and used as a cheap and reliable marker for heparin contamination. We have successfully incorporated this modified test into our hospital's obstetric QC scheme.